Free radicals and senescence

Abstract

There is a significant body of experimental evidence that a rise in intracellular reactive oxygen species (ROS) contributes to senescence. Here we review experiments where entry into senescence has been evaluated in cells whose intracellular ROS levels have been modulated by growth in either high or low ambient oxygen concentrations, or where the cellular antioxidant status has been perturbed. In addition, we discuss the observations that senescence triggered by oncogene expression also appears to be in part mediated by a rise in ROS levels. Finally, we discuss the emerging evidence that in vivo senescence might also be triggered by a rise in cellular oxidant levels. Although these data tend to support a role for ROS in mediating senescence, significant questions remain as to whether ROS act in a random or specific fashion and what precise oxidant species acts as the potential senescence trigger.

Oxidation resistance 1 is a novel senolytic target

“…OXR1 is crucial for protecting cells against oxidative stress by regulating the expression of several enzymes that detoxify ROS (Jaramillo‐Gutierrez, Molina‐Cruz, Kumar & Barillas‐Mury, 2010; Oliver et al., 2011; Yang et al., 2015), and it may be particularly important as a senolytic target of PL because SCs are known to produce high levels of ROS but remain resistant to oxidative stress (Supporting Information Figure S2) (Chandrasekaran, Idelchik & Melendez, 2017; Davalli, Mitic, Caporali, Lauriola & D'Arca, 2016; Lee et al., 1999; Lu & Finkel, 2008). In addition, LMD‐3, homolog of OXR1 in Caenorhabditis elegans , has been shown to protect against oxidative stress and accelerated aging in the worm (Sanada et al., 2014).…”

“…SCs are known to produce high levels of ROS, but they are highly resistant to oxidative stress (Chandrasekaran et al., 2017; Davalli et al., 2016; Lee et al., 1999; Lu & Finkel, 2008). This resistance may be due to the increased expression of OXR1 and its downstream targets in SCs; therefore, OXR1 may be a genuine senolytic target.…”

The essence of senescence: Figure 1.

“…In fact, lowering the oxygen tension can prevent OIS in HDF ) and tissue culture stressinduced senescence in MEFs (Parrinello et al 2003). It is widely assumed that not oxygen itself, but rather ROS produced by mitochondria are involved in senescence (Lu and Finkel 2008;Moiseeva et al 2009). While ROS levels increase in both replicative senescence and OIS (Furumoto et al 1998;Lee et al 1999), treatment of HDF with a sublethal concentration of H 2 O 2 induces senescence (Chen and Ames 1994;Chen et al 1998).…”

“…For instance, the MINK-p38-PRAK pathway is activated in senescence and controls the activation of p16 INK4A and p53, as well as expression of p21 CIP1 , in a p53-independent manner (Wang et al 2002;Bulavin et al 2003;Iwasa et al 2003;Nicke et al 2005;Sun et al 2007). These results not withstanding, although ROS undoubtedly plays an important role in senescence, the nature and mechanism of this contribution remains largely unclear (Lu and Finkel 2008). Major questions include how the increased levels of ROS are generated, and what the cellular targets for ROS in senescence are.…”

Characterization of Human Serum Immunoglobulin G Modified with Singlet Oxygen

“…The carbonyl content of modified IgG is very high as compared to native IgG. The production of superoxide radicals, via immune responses and normal metabolism, is a substantial contributor, if not the primary cause, of pathology associated with neurodegenerative diseases, ischemia reperfusion injury, atherosclerosis and aging [23][24][25]. The assays for generation of hydroxyl radical (OH Á ) and superoxide (O 2 -Á ) were performed [26] to determine the presence of singlet oxygen.…”